B1HA_LOXBO
ID B1HA_LOXBO Reviewed; 278 AA.
AC Q5YD76;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Dermonecrotic toxin LbSicTox-betaIA1a;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Lb3 {ECO:0000303|PubMed:16480957};
DE AltName: Full=Phospholipase D-like;
DE Short=PLD-like;
DE AltName: Full=Sphingomyelin phosphodiesterase D-like protein 3;
DE AltName: Full=Sphingomyelinase D-like;
OS Loxosceles boneti (North American fiddleback spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=283164;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-278, PROTEIN SEQUENCE OF 1-24, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15450925; DOI=10.1016/j.toxicon.2004.06.013;
RA Ramos-Cerrillo B., Olvera A., Odell G.V., Zamudio F., Paniagua-Solis J.,
RA Alagon A., Stock R.P.;
RT "Genetic and enzymatic characterization of sphingomyelinase D isoforms from
RT the North American fiddleback spiders Loxosceles boneti and Loxosceles
RT reclusa.";
RL Toxicon 44:507-514(2004).
RN [2]
RP IMPORTANT SITES FOR ACTIVITY ON SPHINGOMYELIN.
RX PubMed=16480957; DOI=10.1016/j.bbrc.2006.01.123;
RA Murakami M.T., Fernandes-Pedrosa M.F., de Andrade S.A., Gabdoulkhakov A.,
RA Betzel C., Tambourgi D.V., Arni R.K.;
RT "Structural insights into the catalytic mechanism of sphingomyelinases D
RT and evolutionary relationship to glycerophosphodiester
RT phosphodiesterases.";
RL Biochem. Biophys. Res. Commun. 342:323-329(2006).
CC -!- FUNCTION: This toxin does not show activity on sphingomyelin (SM) and
CC does not show dermonecrotic activities (PubMed:15450925). This toxin is
CC a member of dermonecrotic toxins that cleave the phosphodiester linkage
CC between the phosphate and headgroup of certain phospholipids
CC (sphingolipid and lysolipid substrates), forming an alcohol (often
CC choline) and a cyclic phosphate (By similarity). It may act on ceramide
CC phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and
CC lysophosphatidylethanolamine (LPE), but not on lysophosphatidylserine
CC (LPS), and lysophosphatidylglycerol (LPG) (By similarity). It may act
CC by transphosphatidylation, releasing exclusively cyclic phosphate
CC products as second products (By similarity).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-
CC sphingosyl-1,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60648,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:143891, ChEBI:CHEBI:143892;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine = a 1-acyl-sn-glycero-
CC 2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60700,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:58168, ChEBI:CHEBI:143947;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-
CC glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60704,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:64381, ChEBI:CHEBI:143947;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15450925}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15450925}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
CC subfamily. Class IIb sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: The most common activity assay for dermonecrotic toxins
CC detects enzymatic activity by monitoring choline release from
CC substrate. Liberation of choline from sphingomyelin (SM) or
CC lysophosphatidylcholine (LPC) is commonly assumed to result from
CC substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or
CC lysophosphatidic acid (LPA), respectively, as a second product.
CC However, two studies from Lajoie and colleagues (2013 and 2015) report
CC the observation of exclusive formation of cyclic phosphate products as
CC second products, resulting from intramolecular transphosphatidylation.
CC Cyclic phosphates have vastly different biological properties from
CC their monoester counterparts, and they may be relevant to the pathology
CC of brown spider envenomation. {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:A0A0D4WV12, ECO:0000250|UniProtKB:Q4ZFU2}.
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DR EMBL; AY559845; AAT66074.1; -; mRNA.
DR ArachnoServer; AS000151; Sphingomyelinase D (LbSicTox-betaIA1a).
DR BRENDA; 3.1.4.41; 8288.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; IEA:InterPro.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR SUPFAM; SSF51695; SSF51695; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lyase; Magnesium;
KW Metal-binding; Secreted.
FT CHAIN 1..278
FT /note="Dermonecrotic toxin LbSicTox-betaIA1a"
FT /evidence="ECO:0000305|PubMed:15450925"
FT /id="PRO_0000279556"
FT ACT_SITE 12
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT SITE 96
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT SITE 135
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..58
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 54..197
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 278 AA; 31713 MW; 8EDC1E71A0DF35B4 CRC64;
AXRPKPIWDV AHMVNDLELV DEYLGDGANG LELDVAFSDD GTAEKMYHGV PCDCFRSCKR
TETFTKYMDY IRELTTPGNS KFNNNLILLI MDLKLNGIEP NVAYAAGKSV AEKLLSSYWQ
NGESGARAYI VLSLETITRP EFINGFRDAI KASGHEELFE KIGWDFSGNE DLGDIRRVYQ
KYGIDEHIWQ GDGITNCLPR GDYRLTEAMK KKNDPDYKYT EKVYTWSIDK EASIRNALRL
GVDAVMTNYP ARVKSILNES EFSSTHRMAT YEDNPWQK
